Cold-Induced Suppression of Myogenesis in Skeletal Muscle Stem Cells Contributes to Delayed Muscle Regeneration During Hibernation.

Abstract

Mammalian hibernators experience profound cold stress and prolonged physical inactivity during torpor periods; however, it is unclear how skeletal muscle stem cells (satellite cells; SCs) respond to these challenges. In this study, we demonstrated that SCs from a mammalian hibernator, the Syrian hamster, exhibit remarkable resistance to cold-induced cell death, which is associated with intrinsically higher expression of the antioxidant enzyme GPX4, likely contributing to ferroptosis suppression. RNA-seq analysis revealed widespread downregulation of myogenesis-related genes following cold exposure, suggesting suppression of the myogenic program. Consistently, SCs exposed to cold stress exhibited reduced activation and differentiation capacity upon subsequent rewarming, with an increased number of quiescent Pax7-positive/MyoD-negative cells. Muscle regeneration was markedly delayed during hibernation, accompanied by decreased SC activation and macrophage infiltration, suggesting that cold-induced suppression of SC function underlies the limited regenerative capacity in hibernating hamsters. Our results provide insights into the unique physiology of mammalian hibernators: SC viability is preserved, whereas regenerative activity is selectively suppressed during hibernation.